Coccidiosis control compositions and methods of using same



intestinal coccidiosis.

United States Patent 6 3,234 087 COCCIDIOSIS CONTRGI: COMPOSITIONS AND METHODS OF USING SAME George R. Haynes and Marvin Legator, Modesto, Calif,

This invention relates generally to microbiocidal dithiocarbamates. It is particularly concerned with the prevention and treatment of disease caused by microorganisms with novel aryl aliphatic-dithiocarbamaites,

the use of these dithiocarbamates as microbiocides, especially coccidiostats, and with novel compositions containing such dithiocarba-rnates.

Coccidiosis is a common and widespread poultry disease caused by microorganisms, that is, several species of protozoan parasites of the genus :Eimeria, such as E. tenella, E. necatrix, E. acervuline, E. maxima, E. hagani and E. brunetti. E. tenella' is the causative agent of a severe and often fatal infection ofthe caeca of chickens, which is manifested by severe and extensive hemorrhage, accumulation of blood in the caeca, passage of blood in the droppings. E. necatrix attacks the small intestine of the chick causing what is known as Related species of coccidia such as E. meleagridis and E. adenoides are causative organisms of coccidiosis in turkeys. When left untreated, the severe forms of coccidiosis lead to poor weight gain, reducedfeed efficiency and high mortality in fowl. The elimination or control of this disease is, therefore, of paramount importance to the poultry raising industry. Coccidiosis also effects animals as well as poultry, for example, E. zurnii, E. bovis and E. ellipsoidalis are species of rcoccidia which have been described from cattle. There also appear tobe at least seven valid species of coccidiosis in sheep and goats and at least six species of coccidiosis 'in swine. 'So it maybe seen that there is also a need for effective coccidiostats in the animal raising industry.

A principal object of the present invention, therefore, is provided microbiocid'al dithi'ocarbarnates useful for treatment of disease caused by microorganisms. Another object is to provide a new method for preventing and controlling coccidiosis. It is a .further object to provide novel compositions which, when added to poultry and animal feedstu'ifs, are extremely effective in preventing coccidiosis. A still further object is the provision of poultry and animal feedstutfs containing aryl aliphaticdithiocarbamates.

It has now been found that certain aryl aliphatic-dithiocarbama-tes, more particularly, aryl esters of aliphaticdithiocarbamic acids, are very active against protozoa which causes coccidiosis, especially in poultry. These compounds may also be useful in the treatment ofcoccidiosis in animals. As discussed more fully hereinbelow the development of coccidiosis is prevented when small amounts of these'esters are fed to poultry.

The aryl .(substituted and unsubstituted) esters of aliphatic-dlthiocarbamic acids of this invention may be represented by the formula 2,4,5 trinitrophenyl methyldithiocarbamate,

ice

wherein R represents aryl which may be unsubstituted or substituted with simple substituents such as, for example, halo, nitro, amino, alkyl, alkoxy and hydroxy; and R represents aliphatic (acyclic and alicy'clic) i.e., alkyl, cycloalkyl, alkenyl, cycloalkenyl, and alkynyl which may be substituted with simple substituents such as, for example, halo, nitro, amino, cyano and hydroxy. The aryl group contains from 6 to 14 ring carbon atoms, alkyl from 1 to 10 carbon atoms, cycloalkyl from 3 to 8 carbon atoms, alkenyl'frorn 2 to 10 carbon atoms, cycloalkenyl from 3'to 8 carbon atoms, and alkynyl from 2 to 10 carbon atoms. The preferred class of esters are those wherein R representsphenyl and R represents alkyl or alkenyl, particularly unsubstituted phenyl, unsubstituted alkyl and mono-substituted alkenyl. Of this class of esters, those containing alkyl and alkenyl groups of up to 5 carbon atoms are most preferred.

Representative aryl esters of aliphatic-dithiocarbamic acids, i.e., aryl -aliphatic-dithiocarbamates, include, for example, phenyl methyldithiocarbamate, p-chlorophenyl methyldithiocarbam-ate, 2,4,5-trichlorophenyl methyldi- -thiocarbamate, p-tolyl methyldithiocarbarnate, Z-chloro- 4-methylphenyl ethyldithiocarbamate, p-tert-butylphenyl methyldithiocarbamate, o chlorophenylmethyldithiocarbamate, pentachlorophenyl methyl'dithiocarbam'ate, Xylyl methyldithiocarbamate, o tolyl methyldithiocarbamate,

phenyl allyldithiocarbamate, phenyl vinyldithiocarbarnate,

p-aminophenyl methyldithiocarbamate, p bromop-henyl methyldithiocarbamate, m-iodophenyl ethyldithiiocarbamate, m-fluorophenyl methyldithiocarbam-ate, 2-chloro-4- bromophenyl methyldithiocarbamate, 2,4,5 -tribromophenyl methyldithiocarbamate, 2,4,5-triiodophenyl methyldithiocarbamate, p-nitrophenyl methyldithiocarbamate,

2,4,5 triaminophenyl methyldithiocarbamate, 2,3,4-trichlorophenylmethyldithiocarbamate, 3,4,5-tribromophenyl methyldithiocarbarnate, pachlorophenyl ethyldithiocarbamate, p-

bromophenyl propyldithiocarbamate, p-tolyl isopropyldi- 'thiocarbamate, xylyl 'butyldithiocarbamate, p-tolyl isobutyldithiocarbamate, 2,4,5 trichlorophenyl pentyldithiocarbamate, 2,4,5 -tribrom'ophenyl hexyldithiocarbamate, 3,4,5-triiodophenyl heptyldithiocarbamate, phenyl ethyldithiocarbamate, phenyl propyldithiocarbamate, phenyl 'butyldithiocarbama-te, phenyl hexyldithiocarbamate, phenyl heptyldithiocarbamate, phenyl octyldithiocarbamate, p-tert-pentylphenyl cyclohexyldithiocarbamate, Z-naphthyl methyldithiocarbamate, Z-naphthyl ethyldithiocarbamate,

'2-naphti1yl allyldithiocarbamate, l-naphthyl vinyldithiocarbamate, Z-naphthyl cyclopropyldithiocarbamate, 2 napht hyl Z-pentenyldithiocarbamate, 2-anthryl methyldithiocarbamate, Z-anthryl vinyldithiocarbamate, l-anthryl allyldithiocarhamate, Z-anthryl cyclopropyldithiocarbamate, 2-anthryl 1-butynyldithiocarbamate, and the like.

in accordance with the present invention, it has been discovered that aryl esters of aliphatic-dithiocarbamic acids are potent coccidiostats for preventing the development of coccidiosis when administered to poultry. These new coccidiostats are conveniently fed to poultry as a component of the feed of the poultry although they may also be given alone dissolved or suspended in the drinking water. According to a preferred aspect of the invention, novel compositions for the. treatment of coccidiosis are provided which comprise the aryl aliphatic-dithiocarbamates intimately dispersed in or intimately admixed with an inert edible carrier or diluent. By an inert edible" carrier of diluent is meant one that is nonreactive with the active compounds and that may be administered with safety to the poultry to be treated. The carrier or diluent is preferably one that is or may be an ingredient of the poultry feed.

The compositions which are a preferred feature of this invention are the so-called feed supplements in which the aryl aliphatic-dithiocarbarnates are present in .relatively large amounts and which are suitable for addition to the poultry feed either directly or after an intermediate dilution or blending step. Examples of carriers or diluents suitable for such com-positions are poultry feedingredients such as distillers dried. grains, corn meal, citrus meal, fermentation residues, ground oyster shells, Atta-. pulgus clay, wheat shorts, molasses solubles, corncob meal, edible vegetable substances, toasted dehulled soya flour, soybean mill feed, antibiotic mycelia soyagrits,

crushed limestone and the like. The aryl aliphatic-dithiocarbarnate is intimately dispersed or admixed throughout the solid inert carrier by methods such as grinding, stirring, milling or tumbling. By selecting proper diluents and by altering the ratio of carrier to active ingredient,

compositions of any desired .concentration may be .pre- 1 pared. Formulations containing from about 0.1% to about by weight, and preferably from about 0.3%

are particularly suitable for addition to poultry feedstuffs;

those having from about 0.4% to about 1% by weight of coccidiostat are very satisfactory. The active compound is usually dispersed or mixed uniformly in the diluent I but in some instances may. be sorbed on the carrier. Since it is convenient for the feed manufacturer to use about one pound of feed supplement for each ton of finished feed, the preferred concentration in the supplement is usually a function of the level of active ingredi ent desired in the finished feed.

Very low levels of aryl aliphatic-dithiocarbamates in poultry feed are sufficient to afford the poultry good protection against coccidiosis. Preferably the compound is administered to chickens in. an amount equal toabout p.p.m. to about 600 p.p.m. of the daily feed intake. Optimum results are obtained by feeding ata level, of

about 200 p.p.m. to about 400 p.p.rmof the finished feed. For therapeutic treatment of an established coccidial ina fection, higher amounts of aryl aliphatic-dithiocarbamate, i.e., up to about 10 p.p.m. to about 1000 p.p.m. weight of the feed consumed, may be employed. The most advantageous dosage level will, of course, vary somewhat With particular circumstances such as the type andi severity of the coccidial infection to be treated.

For treating poultry, the feed supplement is uniformly dispersed in the poultry feed by suitable mixing or blending The finished feed is one that :contains a procedures. source of fat, protein, carbohydrate, minerals, vitamins and other nutritional factors as well as the aryl aliphaticdithiocarbamate.

In the above discussion. of this invention, emphasis has been placed on solid compositions wherein :the active ingredient is mixed with an edible carrier in a feed supplement, in aso-called premix or in the final poultry feedstuff. This is the preferred method of administering compounds of this invention. An alternate -method of treatment is to dissolve or suspend the aryl. aliphatic-.

dithiocarbamate inthe drinking Water of the poultry. The quantity of coccidiostat which may be administer in this fashion is, of course, limited by the solubility of the product in water or by the quantity that may be suspended in the water without undue settling. Emulsifiers or surface active agents may be employed for this latter purpose.

to about 5% by weight of aryl aliphatic-dithiocarbamate .40 phe'nyl methyldithiocarbamate. This compound has been This invention is not limited to coccidiostatic compositions having only one aryl aliphatic-dithiocarbamate as the sole active ingredient. Also contemplated within its scope is what might be called combined. treatment where two or more of the coccidiostats of this invention are used together. or whereone, two, or more of the. coccidiostats of this invention areadministered concurrently with othercoccidiostats. For such purposes, compositions may be prepared containing, for example, phenyl methyldithiocarbamate and p-chlorophenyl methyldithiocarbamate together, .or phenyl methyldithiocarbamate admixed with one or-more'other known coccidiostats such as sulfaquinoxaline, -4,4'-dinitrocarbanilide-2 hydroxy-4,6-

dimethylpyrimidine complex, 3,3-dinitrodiphenyldisulfide, arsanilicacid, 3-aminol hydroxy-phenylarsonic acid, 5-, nitrofu'rfural'. semicarbazone, and the like.

It will likewise be understood by thoseI skilled in this art that special feed supplement formulations and finished poultry feeds containing vitamins, antibiotics,- growthpromoting agents and other nutritional substances may include the aryl aliphatic-dithiocarbamates of this invention. A typical productof this type is the following:,.

Amount/lbmf supplement,

Phenyl methyldithiocarbamate 100.00 Distillers grains to 1 pound.-

Anespecially' active .coccidiostat of this invention is etfective in controlling E; 'tenella in test chicks when .ad-

ministered in feed at concentration in, the range of, 50 to 200 parts per million. For example, Table 1 herein:

after compares the knowmcoccidiostat, vsulfaquinoxaline.

with phenyl' methyldithiocarbamate.

Briefly, the novel 'aryl aliphatic-dithiocarbamates can be prepared by reacting; an aliphatic-isothiocyanate vwith a corresponding aryl mercapt aniaccordin-g to the followmg. equation:

n'Ncs HSR RS(LJ;NH;-R" wherein R andR' are as herein defined;

The following specific examplesillustrate [the preparatron of typical aryl aliphatic-dithiocarbamates within the purview of this invention.

EXAMPLE I.-p-CHLOROPHENYL METHYL- DIT'HIOCARBAMATE I A. solution ofv 18.3 g; (0.251 mole). of methyl isothiocyanate is 50ml. of ether was added tov a solutionof 36.1. g. (0.25 mole) of p-chlorophenyl mercapatanin ml. of ether. to stand overnight.

Two. drops ofv pyridinel was added andxgthe mixture was heated at reflux for -'two hoursz It was then irradiated with light from a nunfrosted light bulb for3 hours., The ether was distilled from the reaction .flask andthe reactionlmixture. was heated onfthesteam bath'for 4 hours The reaction '.mixture 2 was allowed and allowed to cool. Upon standing overnight the mixture solidified to a white crystalline mass. This material was recrystallized from hexane to yield 43 g. M.P. 113- 114, of p-chlorophenyl rnethyldithiocarbamate as white needles.

Analysis.Calculated: N, 6.4%; Cl, 16.3%. Found: N, 6.4%; Cl, 16.4%.

EXAMPLE II.-2,4,S-TRICHLOROPHENYL METHYLDITHIOCARBAMATE A solution of 21.4 g. (0.1 mole) of 2,4,5-trichlorophenyl mercaptan and 7.3 g. (0.1 mole) of methyl isothiocyanate in 100 ml. of anhydrous ether was allowed to stand at room temperature. The ether was distilled to leave a liquid residue which solidified. Recrystallization from isopropyl alcohol gave crystals of 2,4,5-trichlorophenyl methyldithiocarbamate, M.P. 140-142; yield 16 g. (55% Analysis.Calculated: N, 4.9%; Cl, 37.2%.. Found: 7

N, 4.7%; CI, 37.0%.

EXAMPLE III.p-TOLYL METHYLDI- THIOCARBAMATE S l omNos Urn-@su cameras-@01 1.

A solution of 24.8 g. (0.2 mole) of p-t'olyl mercaptan and 14.6 g. (0.2 mole) of methyl isothiocyanate in 150 ml. of anhydrous ether was allowed to stand at room temperature. The ether was distilled leaving a residue which crystallized on standing. This material was recrystallized from hexane to yield 38 g. (96%), M.P. 93, of p-tolyl methyldithiocarbamate.

Analysis-Calculated: N, 7.1%; S, 32.5%. Found: N, 6.8%; S, 32.9%.

EXAMPLE IV.--p-TERT-BUTYLPHENYL METHYLDITHIOCARBAMATE EXAMPLE V.-0-CHLOROPHENYL METHYLDITHIOCARBAMATE A solution of 41.1 g. (0.284 mole) of o-chlorophenyl merca-ptan and 21.2 (0.29 mole) of methyl isothiocyanate in 150 ml. of ether was allowed to stand at room temperature for 16 hours and the ether was then distilled. The residue very slowly crystallized. Recrystallization from hexane yielded o-chlorophenyl methyldithiocarba- The ether was distilled to leave mate as White needles melting at 86-8"; yield 30 g. (50%).

Analysis.--Calculated: N, 6.4%; C1, 16.3%. Found: N, 6.3%; CI, 16.4%.

EXAMPLE VI.PHENYL METHYL- DITHIOCARBAMATE s H Games @411 animus-Q A solution of 22 g. (0.2 mole) of phenyl mercaptan and 14.6 g. (0.2 mole) of methyl isothiocyanate in 100 ml. of ether was allowed to stand for 16 hours at room temperature. The solution was then heated at reflux for 3 hours and the ether was distilled. The residue which crystallized on cooling was recrystallized from isopropyl alcohol to yield 33 g. M.P. 124, of phenyl methyldithiocarbamate.

Analysis.Calculated: N, 7.7%; S, 35.0%. .Found: N, 7.5%; S, 35.0%.

EXAMPLE VII.PENTACHLOROPHENYL METHYLDITHIOCARBAMATE s I I Q... CH.N..I. O.

All 51 $1 411 A mixture of 28.3 g. (0.1 mole) of pentachlorophenyl mcrcaptan and 7.3 g. (0.1 mole) of methyl isothiocyamate in 800 m1. of anhydrous ether was allowed to stand at room temperature for 16 hours. All of the mercaptan did not dissolve. The mixture was stirred at reflux for 15 hours and the ether was distilled to leave a powdery solid. This solid was pentachlorophenyl methyldithiocarbamate.

Analysis.Calculated: CI, 49.9%; N, 3.9%; S, 18.0%. Found: Cl, 49.7%, 49.7%; N, 3.3%, 3.2%; S, 18.6%.

EXAMPLE VIII.-XYLYL METHYLDI- THIOCARBAMATE I I S I A solution of 20 g. (0.145 mole) of xylyl mercaptan and 10.6 g. (0.145 mole) of methyl isothiocyanate in 150 ml. of anhydrous ether was stirred at room temperature for 4 hours. The ether was removed by distillation to leave a viscous liquid, The liquid was stripped at 0.3 mm. on a steam bath. The residue slowly crystallized as 25 g. of xylyl methyldithiocarbamate (83% of Theor).

Ahalysis.-Calculated for NS C H S, 30.3%; N, 6.6%. Found: S, 27.9%; N, 6.4%.

EXAMPLE IX.o-TOLYL METHYL'DITHIO CARBAMATE S C...N...@ .H CH.NHIIS A solution of 24.8 g. (0.2 mole) of o-tolyl mercaptan and 14.6 g. (0.2 mole) of methyl isothiocyanate in ml. of ether was stirred at room temperature for 6 hours. Evaporation of the ether left a white crystalline solid. This solid was recryst. from hexane to yield 36 g. of o-tolyl methyldithiocarbamate as white needles, M.P. 8990, (90%).

7 8* Analysis.Cal-culated for NS C 'H S, 32.5%; N, f Pounds 7.1%. Found: S, 32.0%; N, 7.0%. p-Chlorophenyl methyldithiocarbarnate. 20.0 EXAMPLE X. PHENYL (2-CYANOALLYL)- i i DITHIOCARBAA/[NYEv Distillers dried grams 50-0 7 o-Tolyl methyldithiocarbamate .25 .0 ON Corn distillers dried grains: 4; 75.0 oHFcHzNcs 2,4,5-trichlorophenyl methyldithiocarbamatei.-, -.s.40.0 Corn meal 60.0 I is, p- Aminophenyl methyldithioca-rbamate. 10.0 Nicarbazin= r r. 15.0 CH2 CCHzNH S Corn ;d1stillers dried gra1'r'1s 75.0 A solution of 22.0 g. (0.2 mole) of benzenethioland pp f are m y mechaHiCal milling '10 ml. of pyridine in 60 m1, of anhydrous ether was m1x1ngof the ingredients to iHSUIC.uI1if0Im.diSlTibUfiO cooled. in an icebath while 24.8 g. (0.2 mole) of l P P 'f Z-cyanoallyl isothiocyanate was added. This solution I The e pew p e Illustrates the f deposited a crystalline precipitate-upon standing'afew tlveness of the vcoccldlfistats of'thlslllventlom hours at room temperature, This precipitate Wasfiltered EXAMPLE XIL+PHENYL METHYLDITHIOCAR; and recrystallized from methanol to yield 31 g. (67%), BAMATEE AND PHENYL (2-CYANOALLYL)-DI- M.P. 106-8, of phenyl (2-cyanoallyl)-dithiocarbamate. 20, THIOCARBAMATE' Analysis.Calculated: N, 12.0%; S, 27.4%. ,Foundz. e Groups 0f loday yoldkchicksl were a :mash diet S, containinglOO to ,400'p.p.m. of. phenylmethyldithiocan EXAMPLE METHYLDI- bamate uniformly dispersed in:the feed. 5 After. having THIOCARBAMATE' been on this ration for.24 hours, each bird was inoculated witlicl cc. of sporulated oocysts of E. tenella, other groups'of 10-day.old chickswere fed a similar mash diet, SH SdNHGHz' containing. no phenylmethyldithiocarbamate.. These were CHQNCS also infected after 24 hours and served ascon-trolse Still other groups of 10-day old chicks were fed the mash diet 30 free of phenyl methyldithiocanbamate and Ewerenot in- A solution of 23.0 g. (0.14 mole) of Z-naphthalenefectedwithcoccidiosis. These servedasnormal controls. thiol, 11.0 g. (0.15 mole) of methyl isothiocyanate and A like test was, runusiug phenyl (2-cyan0allyl)dithiocar.- 10 ml. of pyridine in 50 ml. of anhydrous ether was almlteas he C CCiCliOStat. allowed to stand. overnight at room temperature. A The experiments were completed on t-he seventh day White precipitate formed which was filtered and recrystalafterinjection-y During the seven-day period the infected lized from isopropyl alcohol. The yield of recrystallized birds were observed for clinical evidence of coccidiosisr product was 26 g. (80%), M.P. 128429 The survivingbirdsvwere weighed, sacrificed and'exam- Analysis.Calculated: N, 5.9%; S, 27.1%. Found: ined for cecal coccidiosis. V N, 6.0%; S, 28.1%. i The following resultsiwere :obtained:

Table I Evidence of Concen-- Weight Coccidiosis, day

tration Mortality Increase bleeding after in Feed (percent) per bird. inoculation (pp- 4th 5th 6th Inoculated chick o 50 V 0 M H Non-inoculated chick" 0 0 49 0 0 0 125 25 33 0 M p H 125 12 23 0 s M 50 0 o M 100 0 49 o M s 200 0 41 0 0 0 Do 400 o 41 0 0 0 Phenyl -cyanoallyl) dithiocarbamate 200 0 50 0 S 0 Amount of Bleeding: S=Smal1, M=Mediu.m, H=Higl1.

The following specific examples illustrate compositions containing the novel active ingredients of this invention. Animal and poultry feed supplements having the following compositions are prepared by intimately mixing, for

example, phenyl methyldithiocarbamate and the particu lar edible solid diluent or diluents:

Corn germ meal 30.0 75

In Table .I,it may; be seen that birdslreceiving phenyl methyldithiocarbamate at all concentrations were superior in weight gain and reduced mortality, over those birds receiving Sll1f2.ql1lIl0X3llIl.' It? may; beseen that. no

evidence ofcoccidiosis, .e.g., bleeding, could be :found in birds givenphenyl methyldithiocarbamatex-at 200 ppm. and 400 p.p. m. :in contrast to :those .given sulfaquim oxaline at 125. ppm. It. also may be seen that phenyl (Z-cyanoallyl) dithiocarbamate at 2 00 p.p.rn. showed a weightincreaseof 50 g./ bird with only a small amount ofbleeding on the, 5th day.

Although the ,presentinvention is primarily directed to the use of these aryl aliphatic-dithiocarbamates..ascoccidiostats, they are-alsonsefu-l in controlling a variety of ye-asts, fungi and bacteria as showneby Table II hereinbelow; therefore, these vvuses alsoform a part of .this] invention.

Table 11 Micro Organisms Yeast Fungi Bacteria Dithiocarbamate C. V. P. C. S. M. S. B. L. K. P. P. 8.. E. Albica'ns Albo- Italicum Glo- Rolfsii Avium Aureus Subtz'lus Mesen- Pneu- Aeru- Vul- (1011- 002i atrum bosum term'des nom'ae ginosa gun's inarum p-Chlorophenyl methyldithiocarbamate 0 0 0 0 0 0 0 2,4,5-Trichlorophenyl methyldithiocarbamate 0 0 0 O 0 0 0 O p-Tolyl methyldithiocarbamate 0 0 0 0 0 0 0 0 p-Tert-butylphenylm hyldithiocarhamate 0 0 0 0 0 0 0 0 Phcnyl methyldithiocarbamate 0 0 0 0 0 0 0 0 Ponta chloropheuyl methyldithiocarbarnate 0 0 0 0 O 0 0 0 0 0 Xylyl methyldithiocarbamate 0 :1: :1: :1: =1: :l: o-Tolyl methyldithiocarbamate 0 0 :1: O 0 O 0 Legend:

0=ccmplete control at 50 ppm. i=partial control at 50 ppm. +=no control at 50 p.p.m.

It is to be understood that this invention is not to be limited to the exact details of operation shown and described, as obvious modifications and equivalents will be apparent to one skilled in the art and the invention is, therefore, limited only by the scope of the appended claims.

We claim as our invention:

1. A method of treating coccidiosis in animals and poultry which comprises oral administration of an effective quantity of a dithiocarbamate of the formula:

R is a member of the group consisting of phenyl and phenyl substituted by at least one member of the group consisting of halogen, nitro, amino, alkyl of 1 to 5 carbon atoms, alkoxy of 1 to 5 carbon atoms and hydroxy; and

R is a member of the group consisting of unsubstituted alkyl of 1 to 5 carbon atoms and alkenyl of 2 to 5 carbon atoms substituted by one member of the group consisting of halogen, nitro, amino, cyano and hydroxy.

2. A method of treating coccidiosis in animals and poultry which comprises oral administration of an eifective quantity of S-phenyl N-methyl-dithiocarbamate.

3. A method of treating coccidiosis in poultry which comprises 'oral administration in the feed of at least 50 parts per million by weight of feed of an dithiocarbamate of the formula:

s H res-Lita wherein R is a member of the group consisting of phenyl and phenyl substituted by at least one member of the group consisting of halogen, nitro, amino, alkyl of 1 to 5 carbon atoms, alkoxy of 1 to 5 carbon atoms and hydroxy; and

R is a member of the group consisting of unsubstituted alkyl 'of 1 to 5 carbon atoms and alkenyl of 2 to 5 carbon atoms substituted by one member of the group consisting of halogen, nitro, amino, cyano and hydroxy.

4. A method of treating coccidiosis in poultry which comprises oral administration in the feed of at least 50 parts per million by weight of feed of S-phenyl-N-methyldithi'ocarbamate.

5. A composition useful in the prevention and treatment of coccidiosis in domestic animals which comprises an animal feed and a dithiocarbamate of the formula:

R is a member of the group consisting of phenyl and phenyl substituted by at least one member of the group consisting of halogen, nitro, amino, alkyl of 1 to 5 carbon atoms, alkoxy of 1 to 5 carbon atoms and hydroxy; and

R is a member of the group consisting of unsubstituted alkyl of 1 to 5 carbon atoms and alkenyl of 2 to 5 carbon atoms substituted by one member of the group consisting of halogen, nitro, amino, cyano and hydroxy, the dithiocarbamate making up from 0.1 percent to 10 percent of the total Weight of the composition.

6. A composition useful in the prevention and treatment of coccidiosis in domestic animals which comprises an animal feed and S-phenyl N-methyldithiocarbamate, said dithiocarbamate making up from 0.1 percent to 10 percent of the total weight of the composition.

References Cited by the Examiner UNITED STATES PATENTS Re. 22,750 4/ 1946 Tisdale 167--30 2,610,140 9/1952 Santivasi 16753.1 2,628,183 2/1953 Johnson 16753.1 2,756,249 7/1956 Kirshenbaum 260-455 2,786,866 3/1957 Hook 260--455 2,960,432 11/ 1960 Jones 16730 2,990,319 6/1961 Jones 167--30 3,075,875 1/ 1963 Margot 167-30 FOREIGN PATENTS 96,797 1/ 1961 Netherlands.

OTHER REFERENCES Chabrier: Societe Chimique de France Jan, June 1950, pages 51-65 (particularly pages 51, 58, 59, 61-65).

Links: Chem. Abst. vol. 53, 1959, pages 13486i and 13487a.

JULIAN S. LEVITT, Primary Examiner.

FRANK CACCIAPAGLIA, JR., LEWIS GOTTS,

Examiners. 

1. A METHOD OF TREATING COCCIDIOSIS IN ANIMALS AND POULTRY WHICH COMPRISES ORAL ADMINISTRATION OF AN EFFECTIVE QUANTITY OF A DITHIOCARBAMATE OF THE FORMULA: 